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SARS-CoV-2 Nsp13 encodes for an HLA-E-stabilizing peptide that abrogates inhibition of NKG2A-expressing NK cells.
Hammer, Quirin; Dunst, Josefine; Christ, Wanda; Picarazzi, Francesca; Wendorff, Mareike; Momayyezi, Pouria; Huhn, Oisín; Netskar, Herman K; Maleki, Kimia T; García, Marina; Sekine, Takuya; Sohlberg, Ebba; Azzimato, Valerio; Aouadi, Myriam; Degenhardt, Frauke; Franke, Andre; Spallotta, Francesco; Mori, Mattia; Michaëlsson, Jakob; Björkström, Niklas K; Rückert, Timo; Romagnani, Chiara; Horowitz, Amir; Klingström, Jonas; Ljunggren, Hans-Gustaf; Malmberg, Karl-Johan.
  • Hammer Q; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden. Electronic address: quirin.hammer@ki.se.
  • Dunst J; Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden; Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
  • Christ W; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
  • Picarazzi F; Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy.
  • Wendorff M; Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
  • Momayyezi P; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
  • Huhn O; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
  • Netskar HK; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
  • Maleki KT; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
  • García M; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
  • Sekine T; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
  • Sohlberg E; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
  • Azzimato V; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
  • Aouadi M; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
  • Degenhardt F; Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
  • Franke A; Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
  • Spallotta F; Institute for Systems Analysis and Computer Science "A. Ruberti," National Research Council (IASI-CNR), Rome, Italy.
  • Mori M; Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy.
  • Michaëlsson J; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
  • Björkström NK; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
  • Rückert T; Innate Immunity, Deutsches Rheuma-Forschungszentrum (DRFZ), Institute of the Leibniz Association, Berlin, Germany.
  • Romagnani C; Innate Immunity, Deutsches Rheuma-Forschungszentrum (DRFZ), Institute of the Leibniz Association, Berlin, Germany; Division of Gastroenterology, Infectiology and Rheumatology, Medical Department I, Charité-Universitätsmedizin Berlin, Berlin, Germany.
  • Horowitz A; Department of Oncological Sciences, Precision Immunology Institute, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Klingström J; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
  • Ljunggren HG; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
  • Malmberg KJ; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Cancer Immunology, Institute for Cancer Research, Oslo University Hospital, Oslo,
Cell Rep ; 38(10): 110503, 2022 03 08.
Article in English | MEDLINE | ID: covidwho-1705992
ABSTRACT
Natural killer (NK) cells are innate immune cells that contribute to host defense against virus infections. NK cells respond to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro and are activated in patients with acute coronavirus disease 2019 (COVID-19). However, by which mechanisms NK cells detect SARS-CoV-2-infected cells remains largely unknown. Here, we show that the Non-structural protein 13 of SARS-CoV-2 encodes for a peptide that is presented by human leukocyte antigen E (HLA-E). In contrast with self-peptides, the viral peptide prevents binding of HLA-E to the inhibitory receptor NKG2A, thereby rendering target cells susceptible to NK cell attack. In line with these observations, NKG2A-expressing NK cells are particularly activated in patients with COVID-19 and proficiently limit SARS-CoV-2 replication in infected lung epithelial cells in vitro. Thus, these data suggest that a viral peptide presented by HLA-E abrogates inhibition of NKG2A+ NK cells, resulting in missing self-recognition.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Killer Cells, Natural / Histocompatibility Antigens Class I / Viral Nonstructural Proteins / RNA Helicases / NK Cell Lectin-Like Receptor Subfamily C / SARS-CoV-2 / COVID-19 / Methyltransferases Type of study: Observational study / Prognostic study Limits: Humans Language: English Journal: Cell Rep Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Killer Cells, Natural / Histocompatibility Antigens Class I / Viral Nonstructural Proteins / RNA Helicases / NK Cell Lectin-Like Receptor Subfamily C / SARS-CoV-2 / COVID-19 / Methyltransferases Type of study: Observational study / Prognostic study Limits: Humans Language: English Journal: Cell Rep Year: 2022 Document Type: Article